Sunday, March 17, 2013

Bendamustine and rituximab: the verdict

The results are in. After five cycles of bendamustine (Treanda) and rituximab, which ended in mid-November, I can report that the treatment worked better than I expected.

As you may recall, I entered into it last July feeling a little desperate. My marrow was 90% impacted with CLL, my hemoglobin had dropped into the 7s, my platelets were dipping below 100, and thanks to swollen lymph nodes my abdomen looked like it was ready to give birth to three or four alien babies. You know, the big, ugly Sigourney-Weaver-attacking kind.

When chemo began I did not know what to expect. I knew a CR (complete response) was out of the question. I just hoped I wouldn't get a HAR (half-assed response), one so ultimately poor and useless that it would render all the time, pain, and money not worth it. Especially in someone as heavily pretreated as myself, that kind of response was entirely possible. The disease tends to become more refractory to treatment as time goes on; you don't want a big, ugly failure to confirm your worst fears.

Well, I've now had a follow-up bone marrow biopsy and CT scan. And the bone marrow result was one I did not expect: a CR in the bone marrow, courtesy of a 5-color flow cytometry.

The CLL clones are there, just in numbers too few to analyze. The flow cytometry reveals "no specific diagnostic abnormality." Susupicious B cells comprise "approximately 0.1% of the total cellularity," or "too few to accurately assess clonality."I have to admit that I just about fell out of my chair upon hearing the news. I was hoping, at best, for maybe 20% CLL in the marrow, a significant reduction, to be sure. But not one that pushes my CLL back to pre-diagnosis levels.The CT scan of chest, abdomen and pelvis came out about as well as I might have hoped, but with less stellar results: Numerous swollen nodes are still there, especially in the retroperitoneum of the abdomen. The largest node is 6 x 4 cm, or about 2.4 x 1.6 inches. There are two others about that size, as well as numerous smaller ones.What I am grateful for is that no huge cluster or mass of nodes was found; one can only wonder how bad things must have been at the start of chemo.The spleen was also enlarged, 10 x 6 x 17 cm.

An added bonus on the CT was what wasn't found: "The liver, spleen, gallbladder, pancreas, adrenal glands, and kidneys are unremarkable. . . . Lungs are clear." In other words, no new wrinkles to challenge me on top of the CLL. Four months after therapy my peripheral blood continues to look good, with an absolute lympohoctye count of 0.8, hemoglobin of 12.3, and platelets at 153.Like Caesar's Gaul, CLL is divided into three parts: the marrow, the peripheral blood, and the nodes. It appears that chemo pretty much flushed it out of the first two. It remains a problem and a challenge in the nodes and spleen, which is what I would have expected given my history. And my B2M remains high at 5.1, which indicates the disease won't be staying out of those other two compartments forever.So now, the challenge is maintaining -- or building upon -- the remission I have. I had a good visit with Dr. Thomas Kipps in San Diego in January. More on that in my next post, as well as some thoughts as to where to go from here. But the headline is that the chemo was worth it and that the disease has been dealt a significant blow.

23 comments:

Anonymous
said...

Hi Dave, I have been following your blog for the last 7 years. I am an 8year survivor of cll and still in watch and wait with a steadily increasing wbc. Congrats on your recent results and thanks for your posts, they make me feel less afraid of the future.

Thanks for the update David. I've been following you along time. Hoping for this update. Keep them coming. Currently, I've completed 3 of 6 cycles of PCR. Doc thought I would get the same remission as CR. Thanks a bunch and keep writing.

Thank you Brian for sharing your experiencewith us .Makes me less afraid for the future with cll. Diagnosed 3 years ago with normal blood etc but lots of nodes, all over, clusters too. Cll with 13q, mutated, headed for BR.

Dave, I am glad to hear the good news. I really enjoy your blog and get worried when you go nearly three months without a post. The humor in your writing style is just great! I am a CLL patient too in watch and wait (worry) and I worry less and I am more hopeful learning from warriors like you! Thanks for the update and God bless.

Hi Dave,Thanks for writing, I was worried.My husband is Zap 70 pos, CD38 pos, 11Q del, and unmutated. He had BR and is 18 months into remission. He was not refractory but rather a new patient when he had BR and got the same less than 1% left in the marrow as you! I wish you a long remission.

David, loved the HAR comment, loved hearing about your response, such good news!! Now for a break in the action, you have worked hard, enjoy some time off, greetings to M......love thinking about hat cleaned up marrow..SWEET!Wendy

I had two treatments of BR, the second one was really bad (rash, bad nausea and more for days) but the two treatments were enough to knock me back to normal levels and to watchful waiting. So for me too the chemo was worth it.

Wow, what an information-packed blog. I'm 65 yrs old, I was diagnosed about 3 yrs ago and have been in watch and wait mode. But my last tests showed my wc at 50K and a cat scan showed some swollen abdominal nodes, so I'm about to go see my onco for what will probably be the first round of treatment. It's nice to find a link into the online CLL community. I'm amazed at the depth of your knowledge.

I came by your blog doing research for my father’s disease. He has been diagnosed with CLL 2 years ago and we were in the wait and watch phase. Than, one week ago he just got hemolytic anemia, everything happened so sudden, as he checks his blood work every month. From no treatment we went into a full blown chemo, with Rituximab, cyclophosphamide and prednisone. I felt that my world was falling apart, I thought we will not need treatment for a long time….and now, out of the blue, the anemia…...the chemo…..I was frantically searching for answers……papers, research……medical journals…and I came by your blog. I was deeply moved by your story with the disease and I want you to know…..that your words brought me hope. You know why? Because you are determined to fight it and you are optimistic………I am going to follow your example and…..help my father to make informed choices…..and fight this the best he can!

I wanted to contact you differently, I have some private questions that do not find their place on a webpage. I could not find an e-mail address for you, if you would be so kind to contact me at andradac@yahoo.com, I would greatly appreciate it.

Since I have been personally touched by this disease, I want to do more for people that have to deal with it. So I am starting an NGO that will try to raise funds for CLL research. I believe in the power of mind and I believe than when focused on this, doctors can come up with a cure. Together we’re stronger …. I want my father to win this fight, I want you and all affected by it to win!

Dave, your blog is A-OK. I'm CLL here in the foothils of the Adirondacks. Enlarged spleen but otherwise not much in the way of nodules. Had single agent R for a year; needed more as platelets and hemo and spleen were not so good, Spleen decided to rotate left kidney out of place, etc. Also congestive heart failure for past three years. Funny part is, I almost always feel pretty good. Too dumb to know how screwed up I am, I guess. Started BR; today starts fifth of six treatments, as long as WBC and PLT are high enough. Thanks for your great diary. ...A young 73-yr-old geezer in Northville, NY.

Hey Dave,Great blog and even better news. Have you been considered for or been treated with ibrutinib?I wonder whether anyone out there has sypmtoms like mine (or maybe you've heard from others with similar) - heavy/throbbing/choking but not very large lymph nodes in neck, flu-like malaise, low ALC and not other signs of active disease.Cheers,Ben

Brian recommended you awhile back. I have the CLL passed down by women in our family. I got it at 50. Had HDMP+R @ 51. Now facing a clinical trial @ 53. Found you looking up Castro reviews. Read you about him... love your writing, but worried that if you went through that in 2006 maybe you weren't around anymore, but HOME told me you most certainly are! YES. I've blogged on Caring Bridge but not to the extent you do here and what you provide is incredibly wonderful.

Castro tells me only one woman had one day of nausea with BR. Wow. Doesn't sound that easy. I see you now see Kipps instead. I love how you write about studying up, having long range and short range plans, yet going with your intuition. I know an oncologist who was a whistleblower and wrote books about how screwed up the medical industry is (esp cancer). He says chlorambucil still works the way it worked for 40 years, but of course you can't get it prescribed because there is no money in it.

Hi David,I have just found your blob and i wish I had found it earlier. My Mum was diagnosed with CLL about 15 years ago and has been through 3 rounds of treatment with Fludarabine in that time. Needless to say she cannot have any more of that form of Chemo. She is about to start the BR treatment in 2 weeks, so it is comforting to hear about your testimony on these drugs. She too has en enlarged spleen. It is very hard for me as I live in the USA but all my family is back in England. Thank you so much for sharing.

ME AND MY DIARY

February 2014 in Sedona, AZ, slimmed down to 144 lbs.

My name is David Arenson and I have chronic lymphocytic leukemia. It may kill me. Then again, it may not. Life is full of surprises, although I must admit that this is not the sort of cliffhanger that I had in mind for my 50s.

Until a few years ago, like most people, I had assumed death and disease were the province of old age, not the prime of life. I was just an average person health-wise, and feeling rather fine, thank you. I passed by the occasional wheelchair-bound person or bald-headed chemotherapy patient and didn't think that sort of thing would ever apply to me. The odds were against it, after all. Then, after a blood test at age 46, I became one of those people.

And so, my life has changed. I still enjoy the same things I always have – my beautiful and wonderful soulmate, Marilyn, and music, and walks in the woods, and cheap Asian food at strip malls, and movies in which a giant reptile threatens an entire city.

But I also have a new reality that intrudes, one where mutant B lymphocytes threaten my entire body, and one which requires becoming accustomed to unfamiliar and intimidating territory. My spleen and lymph nodes are swollen and my neck sometimes looks like that of a chipmunk storing too many nuts; bothersome nodes in my left pelvic area are a constant reminder that something is wrong with my body. Over time my immunity has been degraded and I have had to rely more on antibiotics to shake infections that once gave me no pause. I have also experienced the joys of autoimmune hemolytic anemia, of which there are none, which is a scary condition in which the body destroys its own red blood cells, and which leads to fatigue.

My CLL has had more than a physical impact. It has been quite an education -- both in terms of what I have learned about my ability to cope with what once was unthinkable, and in terms of navigating the almost freakishly contradictory world of CLL management and treatment. Needless to say, only a fool treads there without getting the lay of the land; too many local doctors are simply clueless, and even the experts can disagree. I do not claim to have it all figured out, and I expect that I never will, but I am doing my best, and I hope some of my thoughts can be of use to you.

So, if sharing my journey helps you along the way, it will have been my pleasure, something green and growing in this hard, new landscape. We help each other as we can, and this is why we have a vibrant CLL community of websites, forums, and blogs (see links below). The end of the circle is the start of the circle. What goes around comes around.

BLOGGER PROFILE

Writing has been in my blood longer than CLL. I am a former newspaper reporter and editor and co-author with Marilyn of two humor-trivia books, Disco Nixon and Rambo Reagan. Marilyn and I met at the University of California at Santa Cruz and now live in the red rock country of Northern Arizona . . . CLL Diary has been featured in CR, the magazine of the American Association for Cancer Research, and in Family Practice Management, a publication of the American Academy of Family Physicians. Besides writing about CLL, I helped establish CLL Forum, one of the largest discussion groups for patients and caregivers.

CLL PROGNOSTICS & PLANNING

As we patients eventually learn, CLL is not a one-size-fits-all disease. Some cases are indolent, some progressive, some quite aggressive. Prognostic tests can give us a much better idea of what type of CLL we are dealing with. Knowledge is power, and I believe patients should have these tests and know what they mean. They do not provide a complete picture, and sometimes clinical symptoms tell a different story than one might expect from the results, but they are important tools that can help determine the when and what of treatment.

Here are the tests: IgVH mutational status, FISH, ZAP-70 (as done at a research institution such as UC San Diego, not a commercial lab), and CD38.

My tests indicate a progressing disease. I am IgVH unmutated and ZAP-70 positive, as measured at UCSD. I developed an 11q deletion per FISH in 2006, which disappeared in 2012 for some mysterious reason, giving way to a 13q deletion. I am CD38 positive now, despite having been CD38 negative for years.

Given my tender age, I will always be navigating treatment options if I want to have any hope of living a normal life span. Knowing my test results helps me plan ahead, and knowing the possible end point in my battle with CLL helps me plan what treatments make the most sense, and in what order. Like many CLLers, I am encouraged by the progress being made by new drugs such Ibrutinib and ABT-199; not to mention the news that T-cells can be supercharged to wipe out the CLL -- in much the same ferocious way that macrophages went after my red cells during hemolysis with AIHA.

The "when and what" of treatment is a subject of great debate among CLL experts as well as patients and local doctors. I tend to take a conservative approach, ever aware of the fact that overall survival in CLL depends not just on the effectiveness of your first treatment. What you do for an encore -- your ability to respond to treatment again, and then again -- may determine how long you get to stand on the stage. The late CLL expert Dr. Terry Hamblin once wrote that CLL is a war of attrition, and I am ever mindful that such wars are won, if they can be won, slowly.

Whether my decisions ultimately are proved wise will be written in these pages. I began using single-agent rituximab (Rituxan) in 2004, adding the steroid methylprednisolone in March 2007 to combat AIHA. In October 2007, after a severe AIHA relapse that left me steroid refractory, I was treated with Rituxan + cyclophosphamide, vincristine, and prednsione (R-CVP). In January 2009, when AIHA and hemolysis of red blood cells returned, I had Rituxan + cyclophosphamide and dexamethasone (R-CD). I used this a few times to control the condition, with shorter and shorter periods until AIHA relapse. Starting in February 2010 I used Arzerra (ofatumumab) and Revlimid (lenalidomide), and then for a year and a half maintained control of the disease -- and the AIHA -- with Revlimid alone. Alas, the Revlimid came at a high price in terms of blood clotting issues, and as of 2012 I was treated with bendamustine and rituximab, which gave me a CR in the marrow and blood, leaving some swollen lymph nodes behind.

2013 is turning out to be my most challenging year yet, with the arrival of Richter's Transformation in April. Up to 10% of CLL patients can expect to develop Richter's, in which some of the CLL clones mutate into a more dangerous B cell lymphoma. Richter's is fatal in some 50% of cases, but it also can be beaten with chemotherapy and stem cell transplant. Read my latest posts for updates on my experience.

My best advice to patients is to gather all the facts you can about your CLL and then think ahead and plan ahead. Develop a long-term strategy, but expect to have to roll with the punches. And don't be rushed by doctors, family, or anyone else into a decision you are not comfortable with: Treating CLL is almost never an emergency. Take the time to learn and reflect, and then go with your intuition.

There are no guarantees that your choices will work out, of course, but at least you can rest assured that you put your heart and soul into making them. That sort of effort is the effort that can, with luck, beat cancer.

It's a peace sign, or a V for victory, not sure which

Quotes I Like

"The thing in life is not to know all the answers but rather to ask the right questions." -- Anonymous

"Hope is not the conviction that something will turn out well, but the certainty that something makes sense, regardless of how it turns out." -- Vaclav Havel

"The man who never alters his opinion is like standing water, and breeds reptiles of the mind." -- Blake

"We must be willing to let go of the life we have planned so as to have the life that is waiting for us." -- E.M. Forster

"Think of all the beauty still left around you and be happy." -- Anne Frank

“Panic is a projection that is not real. We are not just our fears. Our fears do not necessarily determine our future. This is significant.” -- Greg Anderson, lung cancer survivor

"I had a choice to make when they said I was going to die. I could chose to live the rest of my life dying, or I could chose to live life until I die. And I chose to live life'. -- Anonymous cancer patient

"Life can only be understood backwards; but it must be lived forwards." -- Soren Kierkegaard

A DISCLAIMER

I am not a doctor and I do not play one on the internet. If you take something I say as medical advice and die as a result, perhaps in your next life you will not believe everything you read on the internet.

Copyright 2005-2014 by David Arenson. All rights reserved. Material is for the personal use of CLL patients and caregivers and may not be used or reproduced for commercial purposes.